DESCRIPTION: (Adapted from the application) There is now convincing evidence that high calcium intake can interfere with the ability of high potassium to lower blood pressure. There is also evidence that the level of high Ca at which this interference occurs is greater for women than men. But high Ca is recommended much more often for women. Thus, this phenomenon is especially in need of study on their behalf. However, at present there is no animal model. Previous work by the investigators with hypertensive female Dahl salt sensitive (DS) rats shows that feeding different levels of high oral Ca will activate different BP mechanisms, some antihypertensive but others prohypertensive. Also, the latter can be modulated by the level of sodium as well as Ca in the diet, and most importantly is potentially capable of interfereing with known antihypertensive mechanisms of high oral K. Thus it is hypothesized that by adjustsing both Ca and Na in the diet of female DS rats separate combinations of the two will be uncovered at which the high Ca does interfere with the antihypertensive actcion of high K as well as others at which it does not interfere. This hypothesis will be tested in Aim 1 and, if correct, a future applilcation for funds will be submitted to identify mechanisms responsible for the interfering effect of high Ca. High K is also known to protect vascular endothellial cell functions without lowering BP. This has been seen most often as enhanced EC-dependent relaxation in arteries isolated from high K-fed DS and stroke-prone rats. In the latter, it was found that co-feeding high Ca interfered with this effect of K without affecting BP, but with marked suppression of plasma 1,25dihydroxyvitamin D3 (1.25D). This type of interference by high Ca has not been examined in female DS rats. Thus, in Aim #2 it will be determined if (in the same rats of Aim #1) high Ca interferes with the ability of high K to enhance EC relaxing activity independent of effects on BP. Furthermore, in AIM #3 it will be determined if the ability of high K to enhance EC relaxing activity is dependent on normally high systemic levels of 1,25D as seen in plasma when diet contains only normal, unsupplemented Ca. Supplemental Ca suppresses both PTH and 1,25D, but only 1,25 D through its genomic actions is likely to exert lasting effects on the EC that would remain intact in isolated tissue. 1,25D protects arteries from loss of EC relaxing activity during sustained culture in 1.25D free medium. Parathyroidectomy, which markedly lowers 1,25D, impairs arterial EC relaxing activity in hypertensive rats. These findings suggest a role for 1,25D in normal EC vasorelaxing activity and its maintenance in hypertension. It is proposed that normal plasma levels of 1,25D also play a critical permissive role in mechanisms whereby high oral K enhances EC relaxing activity. If so, it should be possible to restore these mechanisms in high Ca-fed rats by normalizing their plasma 1,25D with direct administration of the hormone. This will be tested in Aim #3 and, if successful, future requests for funds will include more study of this role of 1,25D.